thermomechanical processing routes which introduce high densities of dislocations and interfaces into materials. These defect populations introduce long-range stress fields, enabling substantial strengthening of materials. Thus, processing with the aim to introduce high densities of lattice defects into materials is a wellestablished and efficient method to enhance their strength. [12] Yet, when single-phase metallic materials have few defects such as in the recrystallized state and at the beginning of plastic yielding, they often have insufficient intrinsic lattice friction and thus low flow stress. [13,14] The lattice friction, quantified by the Peierls stress, is a measure of the resistance that an infinite straight dislocation has to overcome when moving from one potential valley to the next. The height of this energy barrier scales with the intrinsic atomic-scale lattice distortions and thus differs profoundly in nature from the long-range stress fields imposed by dense defect populations. In other words, the friction stress describes how severely dislocations are dragged as they move through the distorted Peierls potential landscape of massive solid solutions. In that respect, multiprincipal element solid mixtures, often termed high-or medium-entropy alloys (HEAs or MEAs), provide a very promising material design basis because each individual atom experiences a set of different neighbor atoms creating high and ubiquitous local lattice distortions and stresses. [15,16] In that context, multiprincipal element face-centered cubic (fcc) alloys have the potential for achieving an outstanding yield strength-ductility ratio as they naturally carry high inherent lattice distortions. [15,17,18] However, two key challenges have not been addressed in this context so far. First, the yield strength is low due to the close packed fcc lattice structure. [19][20][21] Second, although the friction stress of these alloys is often higher than in pure metals or binary alloys, it is still usually too close to conventional structural alloys. This means that the level of lattice distortion currently exploited in most substitutional solid solution alloys does not contribute significantly to the yield strength. [20,[22][23][24][25][26][27][28] Here, based on a combined theoretical and experimental approach, we show that the degree of lattice distortion is indeed a key parameter in controlling strengthening mechanisms for the design of hitherto unexplored ultrastrong medium-entropy single-phase alloys. For this purpose, we exploit vanadium (V) as a very efficient element in a Severe lattice distortion is a core effect in the design of multiprincipal element alloys with the aim to enhance yield strength, a key indicator in structural engineering. Yet, the yield strength values of medium-and high-entropy alloys investigated so far do not substantially exceed those of conventional alloys owing to the insufficient utilization of lattice distortion. Here it is shown that a simple VCoNi equiatomic medium-entropy alloy exhibits a near 1 GP...